What are the recommended management strategies for a patient with gout, considering non-pharmacological interventions, medication options, and potential comorbidities such as impaired renal function?

Gout Management

Initial Assessment and Risk Stratification

Start urate-lowering therapy (ULT) immediately in any patient with gout who has tophi, frequent attacks (≥2 per year), chronic kidney disease stage 2 or worse, or past urolithiasis. 1

Before initiating treatment, assess the following:

• Screen for secondary causes of hyperuricemia including medications (thiazide/loop diuretics, low-dose aspirin, calcineurin inhibitors), renal disease, metabolic syndrome, and lead exposure 1
• Measure baseline creatinine clearance to guide drug selection and dosing 1
• Evaluate for uric acid overproduction (24-hour urine uric acid) in patients with gout onset before age 25 or history of kidney stones 1
• Document disease burden including number of attacks per year, presence of tophi on exam or imaging, and chronic symptoms 1

Non-Pharmacologic Management

All gout patients require comprehensive dietary and lifestyle modifications, though these alone are insufficient to achieve target serum urate levels in most patients. 1

Dietary Modifications (Evidence-Based Hierarchy)

Limit:

• Purine-rich meats and seafood (especially organ meats and shellfish) 1, 2
• Alcohol consumption, particularly beer, but also wine and spirits 1
• High-fructose corn syrup sweetened beverages 1, 2

Encourage:

• Low-fat or non-fat dairy products 1, 2
• Vegetables (even high-purine vegetables are safe) 2
• Weight loss if obese 3

Avoid completely:

• Alcohol during acute flares or with inadequate disease control 1

Medication Review

Discontinue non-essential medications that elevate uric acid including thiazide and loop diuretics when alternatives exist for blood pressure control 1, 3. Consider switching to losartan (which has uricosuric effects) or calcium channel blockers 3. Do not discontinue low-dose aspirin for cardiovascular prophylaxis despite modest uric acid elevation 1.

Pharmacologic Urate-Lowering Therapy

Treatment Target

The minimum serum urate target is <6 mg/dL for all patients; lowering below 5 mg/dL may be needed to improve signs and symptoms, particularly in those with tophi. 1, 4

First-Line ULT: Xanthine Oxidase Inhibitors

Allopurinol or febuxostat are first-line agents with equal recommendation strength. 1 Neither is preferentially recommended over the other, though febuxostat lacks safety data in stage 4 or worse CKD 1.

Allopurinol Dosing Protocol

• Start at 100 mg/day for most patients, or 50 mg/day in stage 4 or worse CKD 1
• Titrate upward by 100 mg every 2-5 weeks until target serum urate is achieved 1, 4
• Dose can be raised above 300 mg/day even with renal impairment with adequate patient education and monitoring for toxicity (pruritus, rash, elevated transaminases) 1
• Consider HLA-B*5801 testing before initiation in high-risk populations: Koreans with stage 3 or worse CKD, Han Chinese, and Thai patients regardless of renal function 1

Alternative First-Line: Uricosuric Therapy

Probenecid is an alternative first-line option if XOI is contraindicated or not tolerated. 1

Contraindications to probenecid monotherapy:

• Creatinine clearance <50 mL/min 1
• History of urolithiasis 1
• Elevated urinary uric acid indicating overproduction 1

When using uricosurics:

• Measure urinary uric acid before initiation and monitor during therapy 1
• Consider urine alkalinization with potassium citrate and increased fluid intake 1
• Fenofibrate and losartan have uricosuric effects and can be therapeutically useful components of comprehensive ULT strategy 1

Refractory Disease Management

For patients not achieving target despite maximum XOI dose:

1. Attempt upward dose titration of one XOI to maximum appropriate dose first 1
2. Consider switching between allopurinol and febuxostat for intolerance or after initial titration failure (do not use together) 1
3. Add a uricosuric agent to XOI (probenecid, fenofibrate, or losartan) 1
4. Pegloticase is appropriate for severe disease burden refractory to or intolerant of conventional ULT but is not recommended as first-line therapy 1

Mandatory Flare Prophylaxis During ULT Initiation

All patients starting ULT must receive anti-inflammatory prophylaxis for at least 6 months to prevent mobilization flares. 5, 4

Colchicine Prophylaxis Dosing

Standard dose: 0.5-1 mg daily 5

Dose adjustments for renal impairment:

• CrCl 30-50 mL/min: 0.5 mg daily or every other day 6
• CrCl <30 mL/min (severe): 0.3 mg daily 6
• Dialysis patients: 0.3 mg twice weekly 6

Continue prophylaxis beyond 6 months if:

• Ongoing gout symptoms persist 4
• Tophi remain on physical exam 1
• Patient continues experiencing flares 4

Alternative Prophylaxis

If colchicine is contraindicated or not tolerated:

• Low-dose NSAIDs (if no contraindications) 5, 3
• Low-dose corticosteroids when both colchicine and NSAIDs are contraindicated 5, 3

Acute Flare Management

ULT can be started during an acute attack provided effective anti-inflammatory therapy is instituted. 1 Never stop ULT during acute flares as this perpetuates recurrent attacks 3.

First-Line Acute Treatment Options

NSAIDs are preferred for acute gout when no contraindications exist 2, 7. The key determinant of success is early initiation, not which specific NSAID 7.

Corticosteroids (oral or intra-articular) are appropriate alternatives, particularly with NSAID contraindications 2, 7.

Colchicine for acute flares:

• Standard dose: 1.2 mg (loading), then 0.6 mg one hour later 6
• Do not repeat course more frequently than every 3 days 6
• In severe renal impairment (CrCl <30 mL/min): single 0.6 mg dose, repeat no more than once every 2 weeks 6
• Dialysis patients: single 0.6 mg dose, repeat no more than once every 2 weeks 6

Monitoring Strategy

Monitor serum urate every 2-5 weeks during ULT titration, then every 6 months once target achieved to assess adherence and maintain control 1, 4.

Monitor for allopurinol toxicity including pruritus, rash, and elevated hepatic transaminases, especially during dose escalation 1, 4.

Special Considerations for Renal Impairment

CKD stage 2 or worse is itself an indication for ULT regardless of attack frequency. 1

• Allopurinol remains first-line in renal impairment with appropriate dose adjustment 1
• Probenecid is not recommended as first-line monotherapy when CrCl <50 mL/min 1
• Colchicine requires significant dose reduction in moderate to severe renal impairment 6

Referral Indications

Consider specialist referral for:

• Unclear etiology of hyperuricemia 1
• Refractory signs or symptoms despite appropriate therapy 1
• Difficulty reaching target serum urate with renal impairment after XOI trial 1
• Multiple or serious adverse events from ULT 1

Critical Pitfalls to Avoid

Failure to provide prophylaxis when initiating ULT leads to increased acute attacks and poor medication adherence 5, 3.

Stopping ULT during acute flares perpetuates the cycle of recurrent attacks 3.

Inadequate dose titration of allopurinol (stopping at 300 mg without checking if target achieved) leaves many patients undertreated 1.

Using probenecid in patients with CrCl <50 mL/min or history of kidney stones 1.

Treating acute flares with colchicine in patients already on prophylactic colchicine plus CYP3A4 inhibitors 6.